Kondareddy Cherukula

Multifunctional Inorganic Nanoparticles: Recent Progress in Thermal Therapy and Imaging

Nanotechnology has enabled the development of many alternative anti-cancer approaches, such as thermal therapies, which cause minimal damage to healthy cells. Current challenges in cancer treatment are the identification of the diseased area and its efficient treatment without generating many side effects. Image-guided therapies can be a useful tool to diagnose and treat the diseased tissue and they offer therapy and imaging using a single nanostructure. The present review mainly focuses on recent advances in the field of thermal therapy and imaging integrated with multifunctional inorganic nanoparticles. The main heating sources for heat-induced therapies are the surface plasmon resonance (SPR) in the near infrared region and alternating magnetic fields (AMFs). The different families of inorganic nanoparticles employed for SPR- and AMF-based thermal therapies and imaging are described. Furthermore, inorganic nanomaterials developed for multimodal therapies with different and multi-imaging modalities are presented in detail. Finally, relevant clinical perspectives and the future scope of inorganic nanoparticles in image-guided therapies are discussed.

Polysaccharide-Coated Magnetic Nanoparticles for Imaging and Gene Therapy

Today, nanotechnology plays a vital role in biomedical applications, especially for the diagnosis and treatment of various diseases. Among the many different types of fabricated nanoparticles, magnetic metal oxide nanoparticles stand out as unique and useful tools for biomedical applications, because of their imaging characteristics and therapeutic properties such as drug and gene carriers. Polymer-coated magnetic particles are currently of particular interest to investigators in the fields of nanobiomedicine and fundamental biomaterials. Theranostic magnetic nanoparticles that are encapsulated or coated with polymers not only exhibit imaging properties in response to stimuli, but also can efficiently deliver various drugs and therapeutic genes. Even though a large number of polymer-coated magnetic nanoparticles have been fabricated over the last decade, most of these have only been used for imaging purposes. The focus of this review is on polysaccharide-coated magnetic nanoparticles used for imaging and gene delivery.

Mucoadhesive Chitosan Derivatives as Novel Drug Carriers

Chitosan on its own is a well-established natural polymer and is widely regarded as a biodegradable, biocompatible and nontoxic material for drug delivery applications. Although unmodified chitosan has some mucoadhesive properties on its own, its bioavailability is limited due to its short retention time in the body. Moreover, the high solubility of chitosan at acidic pH levels limits its use for mucosal drug delivery (especially through the oral route). Chemically-modified mucoadhesive chitosan, especially thiolated chitosan, has arisen as an alternative to create novel mucosal drug delivery systems. The mucoadhesive properties that are conferred to the thiolated chitosan certainly set this novel class of second or third-generation thiomers apart. To understand the significance of mucoadhesive chitosan, we first present the mechanism of mucoadhesion and provide comprehensive coverage of description of a variety of chemical modifications to prepare mucoadhesive thiolated chitosan derivatives. We then present the plethora of applications of these modified chitosan variants in a wide range of drug delivery fields, including the delivery of antigens, proteins and genes through a variety of routes, including oral, nasal, pulmonary, vaginal and others. By presenting the range of applications for mucoadhesive chitosan drug carriers we herein demonstrate that chemically-modified thiolated chitosan is a versatile and effective material for a new class of drug delivery vehicles.

CD44 targeting biocompatible and biodegradable hyaluronic acid cross-linked zein nanogels for curcumin delivery to cancer cells: In vitro and in vivo evaluation

Abstract In this study, we developed novel hyaluronic acid cross‐linked zein nanogels (HA‐Zein NGs) to deliver the potential anticancer agent curcumin (CRC), a naturally occurring phytochemical drug in cancer cells. In vitro studies showed that they are highly compatible with the tested cell lines. They showed CD44 specific uptake in CT26 cell line more than by the CD44 receptor pre‐inhibited CT26 cells. The CRC encapsulated HA‐Zein NGs (HA‐Zein‐CRC NGs) found to exert a specific toxicity against CT26 sparing healthy normal fibroblast cells in vitro. The apoptotic effects were further confirmed with flow cytometry showing that the HA‐Zein‐CRC NGs exhibited high anticancer activity against the CT26 cells. The in vivo bio‐distribution with a CT26 tumor model showed their high tumor accumulation thereby improved antitumor efficacy with a low dosage of CRC, compared to the previous reports. Thus, the preclinical studies clearly showed that these novel HA‐Zein NGs would be highly beneficial in encapsulating hydrophobic drugs with improved pharmacokinetics thereby enhancing the therapeutic outcomes. Graphical abstract Figure. No caption available.

Dual-stimuli-responsive albumin-polyplex nanoassembly for spatially controlled gene release in metastatic breast cancer

&NA; Stimuli‐responsive polymeric nanoparticles are useful for overcoming challenges such as transfection efficiency and the specific and safe delivery of genes to cancer cells. Transfection outcomes can be improved through spatially and temporally controlled gene release. We formulated a nanoassembly comprising a disulfide‐crosslinked polyethylenimine (ssPEI) conjugated with a tumor‐specific cell‐penetrating peptide (DS 4‐3) (SPD) polyplex and bovine serum albumin (BSA)‐loaded IR780 (BI) nanoparticle, thereby forming a dual‐stimulus‐triggered, tumor‐penetrating and gene‐carrying nanoassembly (BI‐SPD) via electrostatic complexing. BI‐SPD nanoassembly were composed of highly stable nanosized complexes with an average size of 457 ± 27.5 nm, exhibiting an up to two‐fold enhanced transfection efficiency with no sign of potential cytotoxicity in breast cancer cells. Moreover, upon laser irradiation, a four‐fold increase in transfection efficiency was achieved due to the rapid endosomal escape of polyplexes triggered by the local heat induced by the BI‐SPD nanoassembly. Additionally, the high redox environment in tumor cells facilitated the disassembly of the SPD polyplex for efficient plasmid release in the cytosol. The BI‐SPD nanoassembly also exhibited high penetration and enhanced photothermally triggered gene expression in the 4T1 spheroid model. This BI‐SPD nanoassembly has the potential to enhance the expression of therapeutic genes in tumor models without causing significant toxicity to surrounding healthy tissues, since it has shown higher tumor targeting and accumulation in the 4T1 tumor in mice model. Graphical abstract Dual stimuli responsive nanoassembly was developed by forming complex between the bovine serum albumin loaded IR780 dye with DNA polyplex, which improved the transfection efficiency by photothermally endosomal escape as well as gluthione redox mediated DNA release from polyplex. Additionally, it possess the ability to penetrate the tumor spheroid. Figure. No caption available.

A targeted graphene nanoplatform carrying histamine dihydrochloride for effective inhibition of leukemia-induced immunosuppression

Abstract Despite the introduction of many efficient post-consolidation therapies for complete relapse in leukemia patients, many patients suffer from relapse. Reactive oxygen species (ROS) are considered an important parameter in the immunosuppression of acute myeloid leukemia, where they suppress the cytotoxic action of immune cells such as NK cells and T cells. This study demonstrates a way to achieve effective inhibition of immunosuppression by loading the drug histamine dihydrochloride (HDC) onto graphene quantum dots (GQDs) using hyaluronic acid as a targeting moiety for K-562 cells. The prepared GQD-based nanoplatform was stable and achieved high drug loading on the surface, which resulted in a sustained drug release profile over a period of time. Additionally, the drug-loaded graphene nanoplatform proved to be non-toxic at higher concentrations to K-562 cells and could be effectively taken up into cells due to the targeting moiety. In vitro ROS detection assays proved that the HDC loaded graphene nanoplatform could effectively inhibit ROS and thus prevent the immunosuppression caused by leukemic cells.

Programmed ‘triple-mode’ anti-tumor therapy: Improving peritoneal retention, tumor penetration and activatable drug release properties for effective inhibition of peritoneal carcinomatosis

Peritoneal carcinomatosis (PC) is a fatal condition arising in the gastrointestinal tract. PC patients administered drugs locally in the tumor region, such as in intraperitoneal chemotherapy (IPCh), suffer from low drug retention time and tumor penetration. Herein, we synthesized a lithocholic acid (LCA)-conjugated disulfide-linked polyethyleneimine (ssPEI) micelle (LAPMi) nanoconstruct by covalently conjugating ssPEI and LCA, thereby forming positive charged nanomicellar structures loaded with paclitaxel (PTX) (LAPMi-PTX) for IPCh. The incorporation of a positive surface charge aided in prolonging the peritoneal retention time, presumably via ascites-induced protein corona formation, and the subsequent size expansion caused resistance against undesired clearance through lymphatic openings. Furthermore, preferential tumor penetration by LAPMi-PTX is attributable to the permeation-enhancing properties of LCA, and the subsequent tumor activatable drug release was induced by the presence of disulfide linkages. By integrating these properties, LAPMi exhibited prolonged peritoneal residence time, enhanced tumor permeation and chemotherapeutic effect evidenced by inxa0vitro, tumor spheroid and inxa0vivo studies. Importantly, our strategy enabled significant PC inhibition and increased the overall survival rate of tumor-bearing mice. In conclusion, we provided a new paradigm of intractable PC treatment by enabling the prolonged residence time of the nanoconstruct, thereby enhancing tumor penetration and anti-tumor therapy.

Magnetic field-inducible drug-eluting nanoparticles for image-guided thermo-chemotherapy

Multifunctional nanoparticles integrating cancer cell imaging and treatment modalities into a single platform are recognized as a promising approach; however, their development currently remains a challenge. In this study, we synthesized magnetic field-inducible drug-eluting nanoparticles (MIDENs) by embedding superparamagnetic iron oxide nanoparticles (Fe3O4; SPIONs) and cancer therapeutic drugs (doxorubicin; DOX) in a temperature-responsive poly (lactic-co-glycolic acid) (PLGA) nanomatrix. Application of an external alternating magnetic field (AMF) generated heat above 42u202f°C and subsequent transition of the PLGA polymer matrix (Tgu202f=u202f42-45u202f°C) from the glassy to the rubbery state, facilitating the controlled release of the loaded DOX, ultimately allowing for simultaneous hyperthermia and local heat-triggered chemotherapy for efficient dual cancer treatment. The average size of the synthesized MIDENs was 172.1u202f±u202f3.20u202fnm in diameter. Inxa0vitro studies showed that the MIDENs were cytocompatible and especially effective in destroying CT26 colon cancer cells with AMF application. Inxa0vivo studies revealed that the MIDENs enabled enhanced T2 contrast magnetic resonance imaging and a significant suppression of malignant tumor growth under an AMF. Our multifunctional MIDENs, composed of biocompatible substances and therapeutic/imaging modalities, will be greatly beneficial for cancer image-guided thermo-chemotherapy applications.